Abstract
Dendritic cells (DCs) are professional APCs that traffic to the draining lymph nodes where they present processed antigens to naïve T-cells. The recently discovered triggering receptor expressed on myeloid cells (TREM)-2 has been shown to be expressed on DCs in several disease models, however, its role in asthma is yet to be elucidated. In the present study, we examined the effect of allergen exposure on TREM-2 expression in the airways and on DC subsets in the lung and lymph nodes in murine model of allergic airway inflammation. Sensitization and challenge with ovalbumin reproduced hallmark features of asthma. TREM-2 mRNA expression in the whole lung was significantly higher in the OVA-sensitized and -challenged mice which was associated with increased protein expression in the lungs. Analysis of CD11c+MHC-IIhi DCs in the lung and draining lymph nodes revealed that allergen exposure increased TREM-2 expression on all DC subsets with significantly higher expression in the lymph nodes. This was associated with increased mRNA expression of Th2 and Th17 cytokines. Further analyses showed that these TREM-2+ cells expressed high levels of CCR-7 and CD86 suggesting a potential role of TREM-2 in mediating maturation and migration of DC subsets in allergic airway inflammation.
Highlights
Asthma is a chronic disorder of the conducting airways which involves the interplay of multiple genetic and environmental factors
The recently discovered triggering receptor expressed on myeloid cells (TREM)-2 belongs to a family of cell surface receptors that mediate signaling via associations with the DAP-12 adaptor protein[16]
TREM-2 expression was found to be upregulated on bronchoalveolar lavage fluid cells of patients with pulmonary sarcoidosis[20], and its deficiency on alveolar macrophages resulted in augmented bacterial clearance, decreased bacteremia and improved survival compared to wild type animals[21]
Summary
Asthma is a chronic disorder of the conducting airways which involves the interplay of multiple genetic and environmental factors. DC maturation can be induced by several signaling pathways, such as TLR, Fc receptors and DAP-12 mediated -signaling, based on the activating signal[15]. The recently discovered triggering receptor expressed on myeloid cells (TREM)-2 belongs to a family of cell surface receptors that mediate signaling via associations with the DAP-12 adaptor protein[16]. Viral and bacterial infections, which are known to exacerbate inflammation and impair the lung response in respiratory diseases like asthma, have been associated with increase intracellular and cell surface levels of TREM-2 on macrophages[22,23]. Studies using human DCs have shown that TREM-2 activation, via the DAP-12 pathway, promoted upregulation of CCR-7, partial DC maturation and DC survival through activation of protein tyrosine kinase (PTK) and extracellular signal-regulated kinase (ERK)-mediated signaling[24]. TREM-2 was shown to contribute to mucosal inflammation during colitis with TREM-2−/− DCs displaying lower production of inflammatory cytokines in response to TLR ligands[25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
